The dual glucose‐dependent insulinotropic peptide and glucagon‐like peptide‐1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes

Autor: Jonathan M. Wilson, Axel Haupt, Deborah A. Robins, Marja-Riitta Taskinen, William C. Roell, Giacomo Ruotolo, Jeffrey S. Riesmeyer, Amir Nikooienejad, Kevin L. Duffin
Přispěvatelé: HUS Heart and Lung Center, Clinicum, CAMM - Research Program for Clinical and Molecular Metabolism, Research Programs Unit, University of Helsinki
Rok vydání: 2020
Předmět:
Apolipoprotein B
Endocrinology
Diabetes and Metabolism
Type 2 diabetes
030204 cardiovascular system & hematology
APOC-III
THERAPY
Lipoprotein particle
0302 clinical medicine
Endocrinology
Risk Factors
Medicine
OUTCOMES
Lipoprotein lipase
biology
HEPATIC LIPASE
3. Good health
Cardiovascular Diseases
Original Article
lipids (amino acids
peptides
and proteins)
type 2 diabetes
POLYPEPTIDE RECEPTOR
LIPIDS
medicine.drug
medicine.medical_specialty
Lipoproteins
030209 endocrinology & metabolism
Gastric Inhibitory Polypeptide
Glucagon-Like Peptide-1 Receptor
MECHANISMS
03 medical and health sciences
Insulin resistance
Internal medicine
Internal Medicine
Humans
APOLIPOPROTEIN C-III
Triglycerides
business.industry
Original Articles
medicine.disease
Diabetes Mellitus
Type 2
Heart Disease Risk Factors
LIRAGLUTIDE
3121 General medicine
internal medicine and other clinical medicine
biology.protein
incretin therapy
Dulaglutide
incretin therapy
type 2 diabetes
Hepatic lipase
Insulin Resistance
business
TRIGLYCERIDE-RICH LIPOPROTEINS
Biomarkers
Lipoprotein
Zdroj: Diabetes, Obesity & Metabolism
ISSN: 1463-1326
1462-8902
Popis: Aim To better understand the marked decrease in serum triglycerides observed with tirzepatide in patients with type 2 diabetes, additional lipoprotein-related biomarkers were measured post hoc in available samples from the same study. Materials and Methods Patients were randomized to receive once-weekly subcutaneous tirzepatide (1, 5, 10 or 15 mg), dulaglutide (1.5 mg) or placebo. Serum lipoprotein profile, apolipoprotein (apo) A-I, B and C-III and preheparin lipoprotein lipase (LPL) were measured at baseline and at 4, 12 and 26 weeks. Lipoprotein particle profile by nuclear magnetic resonance was assessed at baseline and 26 weeks. The lipoprotein insulin resistance (LPIR) score was calculated. Results At 26 weeks, tirzepatide dose-dependently decreased apoB and apoC-III levels, and increased serum preheparin LPL compared with placebo. Tirzepatide 10 and 15 mg decreased large triglyceride-rich lipoprotein particles (TRLP), small low-density lipoprotein particles (LDLP) and LPIR score compared with both placebo and dulaglutide. Treatment with dulaglutide also reduced apoB and apoC-III levels but had no effect on either serum LPL or large TRLP, small LDLP and LPIR score. The number of total LDLP was also decreased with tirzepatide 10 and 15 mg compared with placebo. A greater reduction in apoC-III with tirzepatide was observed in patients with high compared with normal baseline triglycerides. At 26 weeks, change in apoC-III, but not body weight, was the best predictor of changes in triglycerides with tirzepatide, explaining up to 22.9% of their variability. Conclusions Tirzepatide treatment dose-dependently decreased levels of apoC-III and apoB and the number of large TRLP and small LDLP, suggesting a net improvement in atherogenic lipoprotein profile.
Databáze: OpenAIRE
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